Project Summary The long-term goal of this work is to improve the understanding of neural mechanisms that underlie acoustic communication. Our premise is that the amygdala, a brain region associated with emotional expression, plays a critical role in this process. The amygdala ?decides? whether a vocal signal is significant, or salient, and whether its valence is positive or negative based on contextual information from the vocal sequence, other senses, and the listener's internal state. The amygdala orchestrates emotional responses that are appropriate for the received vocal communication signals and their context. Further, the amygdala modulates responsiveness to vocal signals through its direct and indirect projections to auditory cortex and other auditory structures. In other words, the amygdala is likely to influence how we hear and respond to social vocalizations. Our central hypothesis is that the basolateral amygdala (BLA) receives information about all types of social vocalizations, and that mechanisms within the BLA provide moment-by-moment assessment of the meaning of these social signals based on the surrounding context. This assessment is expressed by highly selective responses of most BLA neurons for contextually aversive vocal stimuli and by context-dependent temporal patterns of response. We hypothesize that this assessment depends on integration of excitatory auditory inputs with GABAergic inhibition and neuromodulatory inputs. We will examine bases for selectivity, temporal response patterns, and contextual modulation in four Specific Aims. First, we will use intracellular recording to examine subthreshold and suprathreshold responses to vocal stimuli in BLA. Second, we will examine the contributions of auditory cortical and thalamic inputs to the responses of amygdalar neurons, using optogenetic methods to separately inactivate each of these inputs. In the final two Aims, we will combine local application of drugs with single neuron recordings to examine the contributions of receptors mediating glutamatergic excitation and GABAergic inhibition, as well as receptors for cholinergic modulation that are likely to convey contextual information associated with the received social vocalizations. We will use a normal hearing mouse strain, CBA/CaJ, that has a well understood acoustic communication system. These Specific Aims provide an interconnected approach to understand the mechanisms acting within the basolateral amygdala that contribute to the analysis of meaning in social vocalizations. These mechanisms are important in acoustic communication because the amygdala is involved in disorders that result in an altered emotional response to speech, such as schizophrenia, autism, and some forms of post-traumatic stress disorder. Furthermore, these studies will assess mechanisms related to therapeutic drugs affecting glutamatergic, GABAergic, and cholinergic transmission in the amygdala.